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A Study of Venetoclax in Combination With Cobimetinib and Venetoclax in Combination With Idasanutlin in Patients Aged > / = 60 Years With Relapsed or Refractory Acute Myeloid Leukemia Who Are Not Eligible for Cytotoxic Therapy

Trial Status: Active

The primary objective for this study is to assess the safety and tolerability as well as preliminary efficacy of venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients > / = 60 years of age with relapsed or refractory acute myeloid leukemia (R / R) AML who are not eligible for cytotoxic therapy.

Inclusion Criteria

  • Histological confirmation of relapsed or refractory AML after prior anti-leukemic therapy by WHO Classification
  • Not eligible for cytotoxic therapies
  • Ineligible for allogeneic stem cell transplant
  • Life expectancy of at least 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Adequate liver and renal function

Exclusion Criteria

  • Patients with acute promyelocytic leukemia (French-American-British [FAB] class M3 AML)
  • Known active central nervous system (CNS) involvement with AML at study entry
  • ECOG Performance Status (>/=) 3 in patients who are (>/=) 75 years old or ECOG Performance Status of 4, regardless of age
  • Prior exposure to Bcl-2 inhibitors, murine double minute 2 (MDM2) antagonists or prior exposure to experimental treatment targeting Raf, mitogen-activated protein kinase (MEK), or the mitogen-activated protein kinase (MAPK) RAS/RAF/MEK/ERK MAPK pathway
  • Positive for hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and known history of HIV, malignancy, active infection and cardiovascular diseases (CVs)
  • Received strong cytochrome (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers and moderate CYP3A inducers within 7 days prior to initiation of study treatment
  • History of symptomatic Clostridium difficile infection within 1 month prior to dosing Additional phase specific exclusion criteria: Phase Ib Dose Escalation Arm A (Venetoclax and Cobimetinib)
  • History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower Phase Ib Dose-Escalation Arm B (Venetoclax and Idasanutlin): Received the following within 7 days prior to the initiation of study treatment:
  • Strong CYP2C8 inhibitors or CYP2C8 substrates
  • OATP1B1/3 substrates Received the following within 14 days prior to the initiation of study treatment: * Strong CYP2C8 inducers
  • Received hormonal therapy (apart from luteinizing hormone releasing hormone agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks prior to the first dose of study treatment
  • History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
  • Received treatment with oral or parenteral anticoagulants/anti-platelet agents withing 7 days prior to initiation of study treatment. Phase II Expansion Arm A and Arm B:
  • Received the following within 7 days prior to the initiation of study treatment:
  • Strong CYP2C8 inhibitors or CYP2C8 substrates
  • OATP1B1/3 substrates
  • Received the following within 14 days prior to the initiation of study treatment: * Strong CYP2C8 inducers
  • History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/CSCR, RVO, or neovascular macular degeneration
  • LVEF below institutional LLN or below 50%, whichever is lower
  • Received hormonal therapy (apart from luteinizing hormone releasing hormone agonist/antagonist for prostate cancer and hormone replacement therapy) within 2 weeks prior to the first dose of study treatment
  • History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Sacramento
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Colorado

Aurora
University of Colorado Hospital
Status: COMPLETED

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Hoffmann-La Roche

  • Primary ID GH29914
  • Secondary IDs NCI-2016-00260, 2015-003386-28
  • Clinicaltrials.gov ID NCT02670044